galE2 Family assigned · medium auto-curated

H37Rv Rv0501 · MTBC0 mtbc0_000529 · 376 aa · 594995–596125 (+) · RefSeq NP_215050.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)UDP-glucose 4-epimerase GalE
MTBC0 PGAP re-annotationSDR family oxidoreductase
Revised (this work)SDR family oxidoreductase. Pfam: Epimerase (PF01370.28), GDP_Man_Dehyd (PF16363.12), 3Beta_HSD (PF01073.26).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WKT3 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0501

UniProt still lists this protein as Uncharacterized protein Rv0501; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
M Cell wall / membrane / envelope biogenesis
Preferred namegalE2
eggNOG descriptionepimerase dehydratase
Orthologous groupCOG0451
EC number EC 5.1.3.2
KEGG orthology K01784
KEGG pathways map00052, map00520, map01100
KEGG modules M00361, M00362, M00632
Gene Ontology (12) GO:0005575, GO:0005576, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0044424, GO:0044444, GO:0044464, GO:0071944

Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 0.233 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 2 missense, 0 nonsense, 0 frameshift

pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.

Domains (Pfam, hmmscan --cut_ga)

PfamAccessioni-EvalueResiduesDescription
EpimerasePF01370.28 2.7e-2226–256 NAD dependent epimerase/dehydratase family
GDP_Man_DehydPF16363.12 2.4e-1227–160 GDP-mannose 4,6 dehydratase
3Beta_HSDPF01073.26 1.9e-0927–155 3-beta hydroxysteroid dehydrogenase/isomerase family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv0500B (Rv0500B, len: 33 aa. Conserved hypothetical protein. Basic protein 18 of the 33 aa are Arg or Lys, with strong similarity to AL079345|SCE68_), high confidence from genomic context alone (score 790 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0502 hyp hypothetical protein 970 970 ctx neighborhood:882 cooccurence:742
Rv0322 udgA UDP-glucose 6-dehydrogenase UdgA 950 948 coexpression:414 database:900
Rv3809c glf UDP-galactopyranose mutase 969 928 database:900 textmining:589
Rv3634c galE1 UDP-glucose 4-epimerase 920 921 database:900
Rv3468c dTDP-glucose 4,6-dehydratase 916 917 database:900
Rv0993 galU UTP--glucose-1-phosphate uridylyltransferase 910 905 database:900
Rv0618 galTa Rv0618, (MTCY19H5.03c), len: 231 aa (probable partial CDS). Probable galTa, first part of galactose-1-phosphate uridylyltransferase, highly 907 903 database:900
Rv0705 rpsS 30S ribosomal protein S19 819 819 experimental:463 database:574
Rv0682 rpsL 30S ribosomal protein S12 816 808 experimental:463 database:573
Rv0710 rpsQ 30S ribosomal protein S17 805 799 experimental:463 database:578
Rv0707 rpsC 30S ribosomal protein S3 804 797 experimental:463 database:578
Rv0721 rpsE 30S ribosomal protein S5 802 795 experimental:463 database:575
Rv0717 rpsN1 30S ribosomal protein S14 790 791 experimental:436 database:548
Rv0500B Rv0500B, len: 33 aa. Conserved hypothetical protein. Basic protein 18 of the 33 aa are Arg or Lys, with strong similarity to AL079345|SCE68_ 789 790 ctx neighborhood:787
Rv2056c rpsN2 30S ribosomal protein S14 789 790 experimental:436 database:548

STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.

Evidence

  • Legacy H37Rv annotation: UDP-glucose 4-epimerase GalE
  • MTBC0 PGAP product: SDR family oxidoreductase
  • Pfam (hmmscan --cut_ga): Epimerase PF01370.28 (E=3e-22), GDP_Man_Dehyd PF16363.12 (E=2e-12), 3Beta_HSD PF01073.26 (E=2e-09)
  • (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)

Sources

  • Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
  • Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215050.2)
  • Domains: Pfam-A via hmmscan --cut_ga — Epimerase (PF01370.28), GDP_Man_Dehyd (PF16363.12), 3Beta_HSD (PF01073.26)
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021, doi:10.1093/molbev/msab293), eggNOG 5.0 DB (Huerta-Cepas et al. 2019) — OG COG0451
  • Curated reference: UniProt P9WKT3 (SwissProt, reviewed; Evidence at protein level)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 99 functional partner(s); context anchor Rv0500B
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000529|Rv0501|galE2
MSSSNGRGGAGGVGGSSEHPQYPKVVLVTGACRFLGGYLTARLAQNPLINRVIAVDAIAPSKDMLRRMGRAEFVRADIRNPFIAKVIRNGEVDTVVHAAAASYAPRSGGSAALKELNVMGAMQLFAACQKAPSVRRVVLKSTSEVYGSSPHDPVMFTEDSSSRRPFSQGFPKDSLDIEGYVRALGRRRPDIAVTILRLANMIGPAMDTTLSRYLAGPLVPTIFGRDARLQLLHEQDALGALERAAMAGKAGTFNIGADGILMLSQAIRRAGRIPVPVPGFGVWALDSLRRANHYTELNREQFAYLSYGRVMDTTRMRVELGYQPKWTTVEAFDDYFRGRGLTPIIDPHRVRSWEGRAVGLAQRWGSRNPIPWSGLR